Dapagliflozin, an SGLT2 inhibitor, reduces cardiovascular events in heart failure with reduced ejection fraction (HFrEF) independent of glycemic control. Its primary mechanism responsible for this benefit is:
- A Glucosuria-induced osmotic diuresis, reducing preload, and potentially increasing myocardial ketone utilization ✓
- B Reduction of hyperglycemia improves myocardial substrate utilization
- C GLP-1 receptor agonism causing direct cardioprotective effects
- D Inhibition of the renin-angiotensin-aldosterone system
Correct answer: A. Glucosuria-induced osmotic diuresis, reducing preload, and potentially increasing myocardial ketone utilization
Explanation
SGLT2 inhibitors improve heart failure outcomes through multiple mechanisms: glycosuria causes osmotic diuresis and natriuresis (reducing preload/afterload without RAAS activation), reduce visceral adiposity, lower blood pressure, and may shift myocardial energy substrate use toward ketone bodies (more oxygen-efficient than fatty acids), providing direct cardiac benefit. These effects are independent of glucose lowering, explaining benefit in non-diabetic HFrEF patients in EMPEROR-Reduced and DAPA-HF trials.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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